It has long been known that astaxanthin can be prepared from canthaxanthin in low yield via astacin and crustaxanthin. J. Chem. Soc. Chem. Commun. 49 (1967). This process is not suitable for commercial purposes.
From U.S. Pat. No. 4,585,885 it is known that astaxanthin can be prepared in a four-step synthetic sequence from canthaxanthin. The process is indicated to be of commercial value. However, it is apparent that also this process is rather laborious and results in considerable losses and low yields of product.
The reaction sequence as described in U.S. Pat. No. 4,585,885 involves the formation of either an alkylether or a trialkylsilylether as being necessary to protect the initially-formed metal enolate from destruction during the following oxidation reaction which involves the application of an acidic oxidant.
It has recently been described (J. Org. Chem. 49, 3241-3243 (1984)) that trans-2-(phenylsulfonyl)-3-phenyloxaziridine can oxidize certain metal enolates. This oxidizing agent is also known to epoxidize alkene double bonds. Tetrahedron Letters, page 917 (1981).
It is also a well-known fact that carotenoid compounds are extremely sensitive to oxygen and other oxidizing agents, the result being a variety of products rather than any single desired end product. Accordingly, until the present invention, it was not known what effect such an oxidizing agent might have upon the extremely sensitive carotenoid compounds, and especially upon a canthaxanthin compound, particularly a canthaxanthin dienolate, which is employed as a preferred intermediate according to the method of the present invention.
It has now surprisingly been found that astaxanthin can be prepared in a very simple and selective way from canthaxanthin by oxidizing a metal dienolate, a dienamine, or dienolether of canthaxanthin with an oxaziridine oxidant.
The best known method for the production of astaxanthin up until the time of the present invention appears to be that of U.S. Pat. No. 4,585,885, issued Apr. 29, 1986, which produces astaxanthin by a reaction sequence involving four (4) steps, namely, preparation of a lithium enolate, preparation of an alkylsilyl enolether from the lithium enolate, oxidation of the alkylsilyl enolether using a percarboxylic acid, and finally removal of the protecting alkylsilyl groups by hydrolysis. The process of the present invention involves entirely different intermediates than the previous process and does not involve the employment of an alkylsilyl protecting group and removal thereof, consequently shortening the process by the elimination of two (2) steps, thereby rendering the present process more economically efficient, especially since it is conveniently conducted as a single-pot reaction. Moreover, the oxidant employed in the process of the present invention, upon completion of the reaction, is in the form of a compound which is in fact a one-step removed starting material for preparation of the oxidant itself, thereby providing the opportunity for even greater economy by simply recycling the conversion product of the oxidant employed back to produce additional starting oxidant.